The present invention relates to compounds which are useful for the protection of organic compounds comprising at least one guanidino moiety and/or at least one amino group. The invention further relates to a process for the preparation of these compounds and to their use as protecting reagents. The invention also relates to the process for the protecting reaction and to the protected compounds thereof.
Suitable protection of a guanidino moiety is still an unsolved problem in chemistry because of the difficulty to remove the known protecting groups. This applies particularly to peptide chemistry as the natural amino acid arginine, bearing a guanidino moiety, is of great importance for the preparation of numerous drug substances. During the coupling reaction, guanidino protection of arginine is necessary to avoid acylation potentially followed by deguanidation, thus rendering undesired ornithine and δ-lactam formation.
Depending on the coupling strategy, the most commonly used protecting groups for arginine are p-toluenesulfonyl (Tos), 2,2,5,7,8-pentamethylchroman-6-sulfonyl (Pmc) and 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl (Pbf). However, these protecting groups are too acid-stable, thus requiring harsher removal conditions and a longer removal time. Therefore, the known guanidino protecting groups are prone to form by-products on their removal. Particularly problematic is their cleavage in peptides with multiple arginine residues or in peptides containing tryptophan. Carpino et al. (Tetrahedron Letters 1993, Vol. 34, No. 49, 7829-7832) compare the Pbf protecting group with the Pmc protecting group when used for arginine side chain protection.
WO 01/57045 discloses tricyclic sulfames obtained via benzofuran-, benzothiophene- and indole-intermediates.
Löwe et al. describe the synthesis of heterocyclic sulfonylureas, which for example comprise an indole moiety (J. Heterocyclic Chem., 1996, 33, 763-766).
It is an object of the present invention to provide a compound which easily protects the guanidino moiety of an organic compound and which can be easily removed.